Cancer Science最新文献_第3页

Pulmonary Delivery of TCR Bispecific Proteins via Mesenchymal Stem Cells Facilitates Efficient Clearance of Lung Cancers. 通过间充质干细胞向肺输送TCR双特异性蛋白有助于肺癌的有效清除。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-22 DOI: 10.1111/cas.70192

Teng Wei, Wen Cao, Qiangnu Zhang, E Wu, Qineng Li, Lili Ren

{"title":"Pulmonary Delivery of TCR Bispecific Proteins via Mesenchymal Stem Cells Facilitates Efficient Clearance of Lung Cancers.","authors":"Teng Wei, Wen Cao, Qiangnu Zhang, E Wu, Qineng Li, Lili Ren","doi":"10.1111/cas.70192","DOIUrl":"https://doi.org/10.1111/cas.70192","url":null,"abstract":"T-cell receptor (TCR) bispecific proteins represent a pioneering therapeutic modality that harnesses the diverse target recognition capabilities inherent to TCRs while preserving the beneficial characteristics associated with protein therapeutics. However, investigations into TCR bispecific proteins, particularly within the context of lung diseases, remain limited. This study aims to elucidate their potential for the treatment of lung cancer. We employed a humanized murine model to evaluate the efficacy of TCR bispecific proteins in eradicating lung tumors in vivo. Cytotoxic activity was assessed against various lung cancer cell lines, and statistical tests were used to analyze the data. To address concerns regarding toxic side effects from systemic administration, mesenchymal stem cells (MSCs) were explored as vehicles for the targeted delivery of TCR bispecific proteins. Our findings demonstrate that TCR bispecific proteins exhibit substantial cytotoxic activity against a variety of lung cancer cell lines. MSCs, with optimal pulmonary targeting properties, were shown to persist within the lungs for over 7 days. By employing MSCs to locally secrete TCR bispecific proteins, we achieved therapeutic effects comparable to systemic administration without manifestations of immune overactivation in murine subjects. Additionally, we evaluated various cytokine combinations and discovered that the combination of IL-7, IL-21, and TCR bispecific proteins significantly augmented their capacity to eliminate antigen-negative cells in a heterogeneous tumor model. Collectively, our findings suggest that the combinatorial therapy of TCR bispecific proteins and MSCs holds considerable promise for clinical application in the treatment of lung cancer, potentially enhancing therapeutic efficacy while minimizing adverse effects.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Durvalumab Post Concurrent Chemoradiotherapy in Japanese Patients With Limited-Stage Small-Cell Lung Cancer in the Phase 3 ADRIATIC Trial. 在3期亚得里亚海试验中，Durvalumab在日本有限期小细胞肺癌患者的同步放化疗

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-21 DOI: 10.1111/cas.70188

Yoshitaka Zenke, Yoshimasa Shiraishi, Yasushi Goto, Koichi Azuma, Kyoichi Okishio, Hirokazu Ogino, Yoshitsugu Horio, Satoshi Oizumi, Manabu Hayama, Masahiro Nii, Masaya Harada, Helen Mann, Yuka S Olivo, Haiyi Jiang, Suresh Senan

{"title":"Durvalumab Post Concurrent Chemoradiotherapy in Japanese Patients With Limited-Stage Small-Cell Lung Cancer in the Phase 3 ADRIATIC Trial.","authors":"Yoshitaka Zenke, Yoshimasa Shiraishi, Yasushi Goto, Koichi Azuma, Kyoichi Okishio, Hirokazu Ogino, Yoshitsugu Horio, Satoshi Oizumi, Manabu Hayama, Masahiro Nii, Masaya Harada, Helen Mann, Yuka S Olivo, Haiyi Jiang, Suresh Senan","doi":"10.1111/cas.70188","DOIUrl":"https://doi.org/10.1111/cas.70188","url":null,"abstract":"At the first interim analysis of the global, randomized, phase 3, double-blind ADRIATIC trial in patients with limited-stage small-cell lung cancer (LS-SCLC) not progressing after concurrent chemoradiotherapy (cCRT), consolidation durvalumab significantly improved overall survival (OS; hazard ratio [HR] 0.73) and progression-free survival (PFS) by blinded independent central review (BICR; HR 0.76) versus placebo (dual primary endpoints). We report an exploratory analysis in patients enrolled in Japan. Patients received durvalumab 1500 mg (N = 264), durvalumab+tremelimumab 75 mg (4 doses, N = 200; arm remained blinded), or placebo (N = 266) every 4 weeks for ≤ 24 months. Prior cCRT ± prophylactic cranial irradiation (PCI) was per local standards of care. In the Japan subgroup, 19 and 31 patients received durvalumab and placebo, respectively; prior cCRT comprised cisplatin-etoposide/carboplatin-etoposide in 94.7/5.3% and 87.1/12.9% and once-daily/twice-daily radiotherapy in 10.5/89.5% and 0/100%; 52.6% and 58.1% received PCI. Median OS was not reached versus 44.9 months (3-year OS 67.4% versus 58.1%; HR 0.67, 95% CI 0.24-1.62). Median PFS by BICR was 44.2 versus 29.4 months (24-month PFS 59.6% vs. 58.6%; HR 1.05, 95% CI 0.44-2.36); median PFS by investigator assessment (sensitivity analysis) was 44.2 versus 19.7 months (24-month PFS 65.6% vs. 47.0%; HR 0.68, 95% CI 0.28-1.51). With durvalumab and placebo, 21.1% and 19.4% had maximum grade 3-4 adverse events (AEs), 21.1% and 9.7% had AEs leading to treatment discontinuation, and 52.6% and 45.2% had pneumonitis/radiation pneumonitis (grade 3-4: 0% and 6.5%). In conclusion, consolidation durvalumab demonstrated a favorable risk/benefit profile in Japanese patients with LS-SCLC post cCRT. Trial Registration: ClinicalTrials.gov identifier: NCT03703297.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of Chromosome 19 miRNA Cluster and the Tumor-Suppressive Role of miR-517a-3p in Choriocarcinoma. 19号染色体miRNA簇下调及miR-517a-3p在绒毛膜癌中的抑瘤作用

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-21 DOI: 10.1111/cas.70207

Yuki Nishiko, Kosuke Yoshida, Yuko Yasui, Akira Yokoi, Masami Kitagawa, Eri Inami, Masato Yoshihara, Kazumasa Mogi, Yukari Nagao, Satoshi Tamauchi, Nobuhisa Yoshikawa, Kimihiro Nishino, Eiko Yamamoto, Kaoru Niimi, Hiroaki Kajiyama

{"title":"Downregulation of Chromosome 19 miRNA Cluster and the Tumor-Suppressive Role of miR-517a-3p in Choriocarcinoma.","authors":"Yuki Nishiko, Kosuke Yoshida, Yuko Yasui, Akira Yokoi, Masami Kitagawa, Eri Inami, Masato Yoshihara, Kazumasa Mogi, Yukari Nagao, Satoshi Tamauchi, Nobuhisa Yoshikawa, Kimihiro Nishino, Eiko Yamamoto, Kaoru Niimi, Hiroaki Kajiyama","doi":"10.1111/cas.70207","DOIUrl":"https://doi.org/10.1111/cas.70207","url":null,"abstract":"Choriocarcinoma is a rare gynecologic malignancy. MicroRNAs, which are noncoding RNAs approximately 22 nucleotides in length, are known to regulate gene expression and play important roles in various cancers; however, their functions in choriocarcinoma remain largely unknown. This study aimed to identify disease-specific microRNAs involved in choriocarcinoma development. Eleven cases of choriocarcinoma and five cases of complete hydatidiform mole treated at our institution were analyzed. Total RNA was extracted from trophoblast cells in formalin-fixed, paraffin-embedded specimens using laser capture microdissection, and microRNA sequencing was performed. The analysis revealed that 87 microRNAs were significantly upregulated, whereas 28 were downregulated in choriocarcinoma compared to complete hydatidiform mole. Notably, 13 of the 28 downregulated microRNAs belonged to the chromosome 19 microRNA cluster. In vitro experiments demonstrated that overexpression of miR-517a-3p, a representative member of this cluster, significantly suppressed cell proliferation, migration, and invasion in JEG-3 and BeWo cell lines. Further transcriptome sequencing and computational analysis identified SRSF1 as a target gene of miR-517a-3p, which was validated by dual-luciferase reporter assays. Knockdown of SRSF1 also led to significant reductions in proliferation, migration, and invasion, supporting its functional relevance. Immunohistochemical analysis confirmed that SRSF1 protein was highly expressed in choriocarcinoma tissues compared to complete hydatidiform mole. These findings indicate that downregulation of the chromosome 19 microRNA cluster is a characteristic feature of choriocarcinoma and that miR-517a-3p functions as a tumor suppressor by directly regulating SRSF1 expression.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microbial and Metabolic Disorders in Cervical Cancer: Structural Insights, Biomarkers, Mechanisms, and Therapeutic Strategies. 宫颈癌中的微生物和代谢紊乱：结构见解、生物标志物、机制和治疗策略。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-18 DOI: 10.1111/cas.70201

Hong Tao, Luyu Wang, Yi Ding, Lixian Yi, Mutian Han, Mengmeng Gu, Jian Wu

引用次数: 0

Anticancer Effect of the Triphenylphosphonium-Conjugated Quinolone Antibiotics Targeting Mitochondrial DNA Replication. 靶向线粒体DNA复制的三苯基膦偶联喹诺酮类抗生素的抗癌作用。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-16 DOI: 10.1111/cas.70199

Yuming Qiao, Yuki Kida, Xiaoyi Lai, Nobuko Koshikawa, Rie Igarashi, Atsushi Takatori, Keizo Takenaga

{"title":"Anticancer Effect of the Triphenylphosphonium-Conjugated Quinolone Antibiotics Targeting Mitochondrial DNA Replication.","authors":"Yuming Qiao, Yuki Kida, Xiaoyi Lai, Nobuko Koshikawa, Rie Igarashi, Atsushi Takatori, Keizo Takenaga","doi":"10.1111/cas.70199","DOIUrl":"https://doi.org/10.1111/cas.70199","url":null,"abstract":"Antibacterial quinolones are widely used to treat bacterial infections in humans. They inhibit bacterial DNA gyrase and topoisomerase IV, whose analogous enzymes are present in mammalian mitochondria. Quinolones inhibit mitochondrial topoisomerases, thereby leading to mitochondrial DNA (mtDNA) replication suppression and cancer cell death. Meanwhile, high concentrations of quinolones are required to induce cancer cell death, possibly owing to poor delivery to the mitochondria. In this study, we synthesized nalidixic acid (NA) and ciprofloxacin (CFX) conjugated with the mitochondria-targeting moiety triphenylphosphonium (TPP), NX-TPP and CFX-TPP, to enhance mitochondrial delivery and examined their anticancer efficacy. NX-TPP and CFX-TPP markedly reduced the antibacterial activity, although CFX-TPP was more active than NX-TPP. However, both NX-TPP and CFX-TPP significantly induced cell death in colon HT-29, pancreatic MIAPaCa-2, and other cancer cells but not in non-cancerous cells including normal dermal fibroblasts and human vascular endothelial cells at a comparative level. NX-TPP induced necrosis-like cell death characterized by cell membrane ballooning and rupture. Mechanistically, NX-TPP was efficiently incorporated into the mitochondria, leading to increased mitochondrial reaction oxygen species (mtROS) generation and mitophagy, and decreased mtDNA copy number and mitochondrial respiration. NX-TPP inhibited tumor growth in HT-29 and MIAPaCa-2 xenograft mouse models without any apparent adverse effects. These results suggest that mtDNA replication-targeting quinolone derivatives, termed MitoQNs, that exhibit reduced antibacterial activity, thereby decreasing antibiotic resistance induction, and enhanced anticancer efficacy, are candidate drugs for cancer therapy.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer. 使用LIG1和PARP抑制剂治疗前列腺癌的合成致死性联合疗法的发展。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-16 DOI: 10.1111/cas.70194

Masaru Tani, Koji Hatano, Yu Ishizuya, Toshiki Oka, Tomohiro Kanaki, Shunsuke Inoguchi, Akihiro Yoshimura, Yuki Horibe, Yutong Liu, Sassi Nesrine, Yohei Okuda, Akinaru Yamamoto, Toshihiro Uemura, Gaku Yamamichi, Takuji Hayashi, Yoshiyuki Yamamoto, Taigo Kato, Atsunari Kawashima, Takao Yamaguchi, Satoshi Obika, Kosuke Yusa, Norio Nonomura, Keisuke Nimura

{"title":"Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer.","authors":"Masaru Tani, Koji Hatano, Yu Ishizuya, Toshiki Oka, Tomohiro Kanaki, Shunsuke Inoguchi, Akihiro Yoshimura, Yuki Horibe, Yutong Liu, Sassi Nesrine, Yohei Okuda, Akinaru Yamamoto, Toshihiro Uemura, Gaku Yamamichi, Takuji Hayashi, Yoshiyuki Yamamoto, Taigo Kato, Atsunari Kawashima, Takao Yamaguchi, Satoshi Obika, Kosuke Yusa, Norio Nonomura, Keisuke Nimura","doi":"10.1111/cas.70194","DOIUrl":"https://doi.org/10.1111/cas.70194","url":null,"abstract":"Despite advances in androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase inhibitors (PARPIs), metastatic castration-resistant prostate cancer (mCRPC) remains lethal. PARPIs clinical efficacy is limited in patients with homologous recombination repair deficiencies, such as BRCA1/2 mutations, due to resistance. Thus, identifying novel synthetic lethal interactions with PARP may expand treatment options and improve therapeutic efficacy. Here, to identify genes that influence sensitivity to the PARPI olaparib, we conducted a genome-wide CRISPR-Cas9 knockout screening of 18,010 genes in DU145, 22Rv1, and LNCaP prostate cancer cell lines. Our screening identified PARP and LIG1 as synthetic lethality-inducing factors, whereas TP53 conferred resistance to PARPIs. Simultaneous inhibition of LIG1 and PARP increased DNA damage and apoptosis. Additionally, the combination of the LIG1 inhibitor L82-G17 with olaparib exhibited synergistic effects. To the best of our knowledge, we validated this combination therapy in vivo for the first time, suppressing tumor growth in a DU145 xenograft model while minimizing toxicity in normal tissues. Immunohistochemical analysis revealed that LIG1 was overexpressed in CRPC tissues, suggesting its potential as a therapeutic target. This study established LIG1 as a novel synthetic lethality-inducing factor in prostate cancer, showing that L82-G17 enhances the efficacy of olaparib, regardless of the BRCA mutation status. These findings suggest that the combination of PARP and LIG1 inhibitors could be a novel therapeutic strategy for mCRPC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Citrullination in Tumor Metastasis, Inside and Outside the Cells. 瓜氨酸化在肿瘤转移中的作用，细胞内外。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-14 DOI: 10.1111/cas.70197

Takeshi Tomita, Priyanka Sharma, Sachie Hiratsuka

{"title":"Citrullination in Tumor Metastasis, Inside and Outside the Cells.","authors":"Takeshi Tomita, Priyanka Sharma, Sachie Hiratsuka","doi":"10.1111/cas.70197","DOIUrl":"https://doi.org/10.1111/cas.70197","url":null,"abstract":"Tumor metastasis remains a poor prognosis because it occurs in all tissues and is difficult to diagnose or prevent before metastatic tumor nodules form. Metastasis is a multi-step process involving tumor cells, bone marrow-derived cells, and tissue resident cells, making it a biological three-body problem. It has been shown that a pre-metastatic soil/niche (PMN) is formed in metastatic tissue before tumor cells physically appear at the metastatic site, and suppressing this PMN is key to preventing metastasis. Recent studies highlighted the importance of protein citrullination, an irreversible post-translational modification of proteins, in tumor metastasis. Peptidyl arginine deiminase (PADI) catalyzes the modification of arginine to citrulline. In this enzymatic reaction, the amino acid residue's net charge changes, inducing a structural change in the protein. This review discusses the role of protein citrullination in cancer metastasis. Intracellular citrullination regulates gene expression and genome structure by citrullinating RNA polymerase and histones, while extracellular citrullination provides a pro-metastatic environment. These factors play an important role in PMN formation. Additionally, we discuss PADI inhibitors and anti-metastatic immune cells from the viewpoint of metastasis prevention.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response. 卵巢癌和子宫内膜癌中的DNA甲基化：PARP抑制剂和ICI反应的预测和机制作用。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-12 DOI: 10.1111/cas.70189

Shuhei Kitamura, Ayumi Taguchi, Kana Tamai, Yoko Yamamoto, Anh Quynh Duong, Daisuke Yoshimoto, Ayako Mori, Aya Ishizaka, Saki Tsuchimochi, Kenbun Sone, Masahito Kawazu, Katsutoshi Oda, Yasushi Hirota

{"title":"DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response.","authors":"Shuhei Kitamura, Ayumi Taguchi, Kana Tamai, Yoko Yamamoto, Anh Quynh Duong, Daisuke Yoshimoto, Ayako Mori, Aya Ishizaka, Saki Tsuchimochi, Kenbun Sone, Masahito Kawazu, Katsutoshi Oda, Yasushi Hirota","doi":"10.1111/cas.70189","DOIUrl":"https://doi.org/10.1111/cas.70189","url":null,"abstract":"Cancer treatment is shifting from an organ-based approach to one driven by biological phenotypes, emphasizing the need to understand molecular mechanisms. DNA methylation plays a pivotal role in tumor biology, not only through gene silencing but also by inducing distinct behaviors beyond genetic mutations. In gynecologic cancers, molecular diagnostics, such as homologous recombination deficiency status guiding poly(ADP-ribose) polymerase (PARP) inhibitor therapy in ovarian cancer and deficient mismatch repair/microsatellite instability-high status informing immune checkpoint inhibitor (ICI) therapy in endometrial cancer have already been used in clinical practice. However, tumors with epigenetically driven functional deficiencies, such as BRCA1 promoter methylation in homologous recombination-deficient ovarian cancers or MLH1 promoter methylation in deficient mismatch repair/microsatellite instability-high endometrial cancers, often exhibit poorer prognoses and reduced therapeutic responses compared to their genetically mutated counterparts. Given the unique impact of DNA methylation, precise detection is crucial. Integrating methylation analysis into molecular classification could refine diagnostics-both by identifying mechanistic contributors to treatment response and by serving as predictive biomarkers for therapy selection-thereby optimizing patient management. This review explores the role of DNA methylation in modulating responses to PARP inhibitors and ICIs, highlights its promise as a biomarker in precision oncology, and outlines current developments and clinical challenges in BRCA1 and MLH1 methylation assays.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and Safety of T-DXd in HER2+ and Low/Zero Metastatic BCBM: A Retrospective Multicenter Real-World Study. T-DXd治疗HER2+和低/零转移性BCBM的疗效和安全性：一项回顾性多中心真实世界研究

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-11 DOI: 10.1111/cas.70181

Qingru Zhou, Yuanyuan Li, Ni He, Guorong Zou, Mengqian Ni, Lulu Zhang, Shu Dun, Zhanhong Chen, Kejun Liu, Yabing Cao, Jiajia Huang, Fei Xu, Zhongyu Yuan, Shusen Wang, Yanxia Shi, Yonggao Mou, Anli Yang, Lixia Li, Xin An

{"title":"Efficacy and Safety of T-DXd in HER2+ and Low/Zero Metastatic BCBM: A Retrospective Multicenter Real-World Study.","authors":"Qingru Zhou, Yuanyuan Li, Ni He, Guorong Zou, Mengqian Ni, Lulu Zhang, Shu Dun, Zhanhong Chen, Kejun Liu, Yabing Cao, Jiajia Huang, Fei Xu, Zhongyu Yuan, Shusen Wang, Yanxia Shi, Yonggao Mou, Anli Yang, Lixia Li, Xin An","doi":"10.1111/cas.70181","DOIUrl":"https://doi.org/10.1111/cas.70181","url":null,"abstract":"Accumulating data demonstrate the robust overall and intracranial activity of trastuzumab deruxtecan (T-DXd) in HER2-positive breast cancer brain metastasis (BCBM). Limited data are available on HER2-low/zero BCBM, as well as patients with symptomatic active BM, leptomeningeal disease (LMD), and poor performance status. This multicenter, retrospective, real-world study enrolled patients diagnosed with HER2-positive or low/zero BCBM receiving T-DXd. Progression-free survival (PFS), intracranial progression-free survival (IC-PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), IC-ORR, IC-DCR, and adverse events (AEs) were evaluated. From January 2020 to July 2024, 58 HER2-positive and 30 HER2-low/zero patients were enrolled. In the HER2-positive cohort, the median PFS, IC-PFS, and OS were 11, 13, and 46 months, respectively. ORR and DCR were 65.2% and 91.3% systemically, with IC-ORR and IC-DCR of 61.0%/90.2% (RECIST 1.1) and 59.5%/88.1% (RANO-BM). In the HER2-low/zero cohort, median PFS, IC-PFS, and OS were 4, 5, and 26 months. ORR and DCR were 33.3% and 66.7%. IC-ORR and IC-DCR were 44.4% and 88.9% by RECIST 1.1 and RANO-BM. HR+/HER2-low patients had significantly longer PFS than HR-/HER2-low (10 vs. 3 months, p < 0.001). In the LMD cohort, the 12-month IC-PFS rates were 67.7% and 60.0% in HER2-positive and low/zero cohorts. The most common AEs included fatigue (45.9%) and appetite loss (25.2%). Seven (8.0%) patients suffered interstitial lung disease (ILD), including 2 (2.3%) grade 3. T-DXd showed substantial and durable overall and intracranial efficacy in HER2-positive and low/zero BCBM, including challenging subgroups with active BM or LMD.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-Density Lipoprotein Receptor-Related Protein 11 Promotes Proliferation in Lung Adenocarcinoma. 低密度脂蛋白受体相关蛋白11促进肺腺癌的增殖。

IF 4.3 2区医学

Cancer Science Pub Date : 2025-09-10 DOI: 10.1111/cas.70193

Takumi Kiwaki, Hiroyuki Tanaka, Makiko Kawaguchi, Yoshiko Umekita, Koji Yamamoto, Tsuyoshi Fukushima, Hiroaki Kataoka, Yuichiro Sato

{"title":"Low-Density Lipoprotein Receptor-Related Protein 11 Promotes Proliferation in Lung Adenocarcinoma.","authors":"Takumi Kiwaki, Hiroyuki Tanaka, Makiko Kawaguchi, Yoshiko Umekita, Koji Yamamoto, Tsuyoshi Fukushima, Hiroaki Kataoka, Yuichiro Sato","doi":"10.1111/cas.70193","DOIUrl":"https://doi.org/10.1111/cas.70193","url":null,"abstract":"Low-density lipoprotein receptor-related protein 11 (LRP11) is reported to be overexpressed in various cancers; however, its functional role in lung adenocarcinoma remains poorly understood. This study aimed to elucidate the tumor-promoting function of LRP11 in lung adenocarcinoma. We assessed the expression and function of LRP11 in lung adenocarcinoma cell lines through both silencing and overexpression experiments. RNA sequencing was performed to identify genes associated with LRP11 expression. The clinical relevance was evaluated using public datasets (The Cancer Genome Atlas and the Singapore Oncology Data Portal). LRP11 was overexpressed in lung adenocarcinoma cells and promoted their proliferation in vitro. RNA sequencing identified multiple genes negatively correlated with LRP11, all of which contained predicted C/EBPβ binding motifs in their promoter regions. Clinically, high LRP11 expression was associated with poor prognosis in patients with lung adenocarcinoma. In conclusion, LRP11 promotes lung adenocarcinoma progression by enhancing cell proliferation and modulating transcriptional activity. These findings suggest that LRP11 may serve as a potential therapeutic target and prognostic biomarker in lung adenocarcinoma.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0